tbuckley/cabot-search huggingface dataset:
Serologic Screening for Genital Herpes Infection
Authors: Carol M. Mangione, Michael J. Barry, Wanda K. Nicholson, Michael Cabana, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Katrina E. Donahue, Carlos Roberto Jaén, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, John M. Ruiz, James Stevermer, John B. Wong
Journal: JAMA (2023)

Genital herpes is a common sexually transmitted infection caused by 2 related viruses, herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2). Infection is lifelong; currently, there is no cure for HSV infection. Antiviral medications may provide clinical benefits to symptomatic persons. Transmission of HSV from a pregnant person to their infant can occur, most commonly during delivery; when genital lesions or prodromal symptoms are present, cesarean delivery can reduce the risk of transmission. Neonatal herpes infection is uncommon yet can result in substantial morbidity and mortality.To reaffirm its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on targeted key questions to systematically evaluate the evidence on accuracy, benefits, and harms of routine serologic screening for HSV-2 infection in asymptomatic adolescents, adults, and pregnant persons.Adolescents and adults, including pregnant persons, without known history, signs, or symptoms of genital HSV infection.The USPSTF concludes with moderate certainty that the harms outweigh the benefits for population-based screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant persons.The USPSTF recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant persons. (D recommendation).
Polymer‐Based mRNA Delivery Strategies for Advanced Therapies
Authors: Wenqian Yang, Lucas Mixich, Eger Boonstra, Horacio Cabral
Journal: Advanced Healthcare Materials (2023)

Abstract Messenger RNA (mRNA)‐based therapies offer great promise for the treatment of a variety of diseases. In 2020, two FDA approvals of mRNA‐based vaccines have elevated mRNA vaccines to global recognition. However, the therapeutic capabilities of mRNA extend far beyond vaccines against infectious diseases. They hold potential for cancer vaccines, protein replacement therapies, gene editing therapies, and immunotherapies. For realizing such advanced therapies, it is crucial to develop effective carrier systems. Recent advances in materials science have led to the development of promising nonviral mRNA delivery systems. In comparison to other carriers like lipid nanoparticles, polymer‐based delivery systems often receive less attention, despite their unique ability to carefully tune their chemical features to promote mRNA protection, their favorable pharmacokinetics, and their potential for targeting delivery. In this review, the central features of polymer‐based systems for mRNA delivery highlighting the molecular design criteria, stability, and biodistribution are discussed. Finally, the role of targeting ligands for the future of RNA therapies is analyzed.
Polymerase-δ-deficiency as a novel cause of inborn cancer predisposition associated with human papillomavirus infection
Authors: Johanna Strobl, Bettina Huber, Raul Jimenez Heredia, Reinhard Kirnbauer, Kaan Boztug, Georg Stary
Journal: British Journal of Dermatology (2023)

Our study illustrates a predisposition to cancer upon cutaneous β genus human papillomavirus (HPV) infection as part of human polymerase-δ deficiency. In addition, polymerase-δ deficiency infers susceptibility to the development of large cutaneous warts and progression to squamous cell carcinoma associated with HPV63, which usually causes benign papillomas. Our findings warrant close monitoring for viral skin oncogenesis in individuals with syndromic polymerase-δ deficiency.
SARS-CoV-2 Infection and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents
Authors: Renin Chang
Journal: JAMA (2023)

To the Editor I have several concerns about the recent study1 that found no significant association of SARS-CoV-2 infection with autoimmunity related to type 1 diabetes in groups of children and adolescents from Colorado and from Bavaria, Germany.
Association of COVID-19 Vaccination With Risk for Incident Diabetes After COVID-19 Infection
Authors: Alan C. Kwan, Joseph E. Ebinger, Patrick Botting, Jesse Navarrette, Brian Claggett, Susan Cheng
Journal: JAMA Network Open (2023)

This cohort study compares the risk of new-onset hypertension, hyperlipidemia, and diabetes before and after COVID-19 infection among patients who were vaccinated vs unvaccinated before infection.
Association of Sociodemographic Characteristics With 1-Year Hospital Readmission Among Adults Aged 18 to 55 Years With Acute Myocardial Infarction
Authors: Chinenye M. Okafor, Cenjing Zhu, Valeria Raparelli, Terrence E. Murphy, Andrew Arakaki, Gail D’Onofrio, Sui W. Tsang, Marcella Nunez Smith, Judith H. Lichtman, John A. Spertus, Louise Pilote, Rachel P. Dreyer
Journal: JAMA Network Open (2023)

Importance Among younger adults, the association between Black race and postdischarge readmission after hospitalization for acute myocardial infarction (AMI) is insufficiently described. Objectives To examine whether racial differences exist in all-cause 1-year hospital readmission among younger adults hospitalized for AMI and whether that difference retains significance after adjustment for cardiac factors and social determinants of health (SDOHs). Design, Setting, and Participants The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study was an observational cohort study of younger adults (aged 18-55 years) hospitalized for AMI with a 2:1 female-to-male ratio across 103 US hospitals from January 1, 2008, to December 31, 2012. Data analysis was performed from August 1 to December 31, 2021. Main Outcomes and Measures The primary outcome was all-cause readmission, defined as any hospital or observation stay greater than 24 hours within 1 year of discharge, identified through medical record abstraction and clinician adjudication. Logistic regression with sequential adjustment evaluated racial differences and potential moderation by sex and SDOHs. The Blinder-Oaxaca decomposition quantified how much of any racial difference was explained and not explained by covariates. Results This study included 2822 participants (median [IQR] age, 48 [44-52] years; 1910 [67.7%] female; 2289 [81.1%] White and 533 [18.9%] Black; 868 [30.8%] readmitted). Black individuals had a higher rate of readmission than White individuals (210 [39.4%] vs 658 [28.8%], P &amp;amp;lt; .001), particularly Black women (179 of 425 [42.1%]). After adjustment for sociodemographic characteristics, cardiac factors, and SDOHs, the odds of readmission were 34% higher among Black individuals (odds ratio [OR], 1.34; 95% CI, 1.06-1.68). The association between Black race and 1-year readmission was positively moderated by unemployment (OR, 1.68; 95% CI, 1.09- 2.59; P for interaction = .02) and fewer number of working hours per week (OR, 1.01; 95% CI, 1.00-1.02; P for interaction = .01) but not by sex. Decomposition indicates that 79% of the racial difference in risk of readmission went unexplained by the included covariates. Conclusions and Relevance In this multicenter study of younger adults hospitalized for AMI, Black individuals were more often readmitted in the year following discharge than White individuals. Although interventions to address SDOHs and employment may help decrease racial differences in 1-year readmission, more study is needed on the 79% of the racial difference not explained by the included covariates.
Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life
Authors: Masayuki Hata, Maki Hata, Elisabeth M.M.A. Andriessen, Rachel Juneau, Frédérique Pilon, Sergio Crespo-Garcia, Roberto Diaz-Marin, Vera Guber, Francois Binet, Frédérik Fournier, Manuel Buscarlet, Caroline Grou, Virginie Calderon, Emilie Heckel, Heather J. Melichar, Jean-Sebastien Joyal, Ariel M. Wilson, Przemyslaw Sapieha
Journal: Journal of Clinical Investigation (2023)

Pathological neovascularization in age-related macular degeneration (nvAMD) drives the principal cause of blindness in the elderly. While there is a robust genetic association between genes of innate immunity and AMD, genome-to-phenome relationships are low, suggesting a critical contribution of environmental triggers of disease. Possible insight comes from the observation that a past history of infection with pathogens such as Chlamydia pneumoniae, or other systemic inflammation, can predispose to nvAMD in later life. Using a mouse model of nvAMD with prior C. pneumoniae infection, endotoxin exposure, and genetic ablation of distinct immune cell populations, we demonstrated that peripheral infections elicited epigenetic reprogramming that led to a persistent memory state in retinal CX3CR1+ mononuclear phagocytes (MNPs). The immune imprinting persisted long after the initial inflammation had subsided and ultimately exacerbated choroidal neovascularization in a model of nvAMD. Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identified activating transcription factor 3 (ATF3) as a central mediator of retina-resident MNP reprogramming following peripheral inflammation. ATF3 polarized MNPs toward a reparative phenotype biased toward production of proangiogenic factors in response to subsequent injury. Therefore, a past history of bacterial endotoxin-induced inflammation can lead to immunological reprograming within CNS-resident MNPs and aggravate pathological angiogenesis in the aging retina.
Angioimmunoblastic T‐cell lymphoma presenting with severe plasmacytosis mimicking plasma cell leukemia
Authors: Mateo Mejia Saldarriaga, Mohammad Alhomoud, Gail Roboz, John N. Allan, Jia Ruan, Madhu M. Ouseph, Paul D. Simonson, Mark Bustoros, Ruben Niesvizky
Journal: American Journal of Hematology (2023)

Peripheral blood smear (A) demonstrates increased numbers of plasma cells (representative cells indicated by arrows), (B) demonstrates polytypic nature of plasma cells.
Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Sammy Ferri-Borgogno, Ying Zhu, Jianting Sheng, Jared K. Burks, Javier A. Gomez, Kwong Kwok Wong, Stephen T.C. Wong, Samuel C. Mok
Journal: Cancer Research (2023)

Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all ovarian cancer deaths. Nevertheless, 15% of patients diagnosed with advanced HGSC survive more than 10 years. The elucidation of predictive markers of these long-term survivors (LTS) could help identify therapeutic targets for the disease, and thus improve patient survival rates. To investigate the stromal heterogeneity of the tumor microenvironment (TME) in ovarian cancer, we used spatial transcriptomics to generate spatially resolved transcript profiles in treatment-naïve advanced HGSC from LTS and short-term survivors (STS) and determined the association between cancer-associated fibroblasts (CAF) heterogeneity and survival in patients with advanced HGSC. Spatial transcriptomics and single-cell RNA-sequencing data were integrated to distinguish tumor and stroma regions, and a computational method was developed to investigate spatially resolved ligand-receptor interactions between various tumor and CAF subtypes in the TME. A specific subtype of CAFs and its spatial location relative to a particular ovarian cancer cell subtype in the TME correlated with long-term survival in patients with advanced HGSC. Also, increased APOE-LRP5 cross-talk occurred at the stroma-tumor interface in tumor tissues from STS compared with LTS. These findings were validated using multiplex IHC. Overall, this spatial transcriptomics analysis revealed spatially resolved CAF-tumor cross-talk signaling networks in the ovarian TME that are associated with long-term survival of patients with HGSC. Further studies to confirm whether such cross-talk plays a role in modulating the malignant phenotype of HGSC and could serve as a predictive biomarker of patient survival are warranted.Generation of spatially resolved gene expression patterns in tumors from patients with ovarian cancer surviving more than 10 years allows the identification of novel predictive biomarkers and therapeutic targets for better patient management. See related commentary by Kelliher and Lengyel, p. 1383.
Cross-cultural adaptation and psychometric properties of the Brazilian Portuguese version of the Impact of Neurofibromatosis type 1 on Quality of Life (INF1-QoL) questionnaire
Authors: Natália P Bicudo, Carla Maria Ramos Germano, Lucimar R S de Avó, Rosalie E Ferner, Débora G Melo
Journal: British Journal of Dermatology (2023)

This study aimed to adapt the Impact of Neurofibromatosis Type 1 on Quality of Life (INF1-QoL) questionnaire to Brazilian Portuguese and assess its psychometric properties. The INF1-QoL was adapted using a translation-back-translation method, and a pretest was conducted with 101 adults with NF1. Cronbach’s α revealed that the INF1-QoL questionnaire was reliable (0.801). An exploratory factor analysis uncovered two latent factors, which explained 49% of the variance in the results. The factor structure provided adequate composite reliability indices, replicability estimates and goodness-of-fit indices. The INF1-QoL questionnaire was translated, adapted and validated in the Brazilian context. It is a useful patient-reported outcome measure for NF1 healthcare providers in Brazil.
Outcomes of periodontal therapy: Strengthening the relevance of research to patients. A co‐created review
Authors: Ian Needleman, Neil Almond, Natalie Leow, Jim Phillips
Journal: Periodontology 2000 (2023)

Abstract Periodontitis is a long‐term condition affecting up to half of the population globally and causing significant impacts on life quality. Successful management depends on taking life‐long ownership of the condition by those affected. There is a wealth of research to inform on management options. However, most of the research has been designed by professional experts with outcomes to gauge benefits and harms based on parameters that inform on the disease process but which might not be informative to support decision‐making in people with lived experience (PWLE) of periodontal ill‐health (including both patients and carers). The importance of relevant outcomes is highlighted in the concept of the “expert patient” which aims to strengthen the capacity of PWLE to make health‐care choices that are important for them, elements of which are likely to be already familiar to many clinicians delivering periodontal health care. Therefore, the voice and collaboration of PWLE in research are recognised as crucial to developing high quality, relevant evidence especially for long‐term conditions. In this paper, we review what is known about the relevance of treatment outcomes to PWLE. We also examine the degree to which PWLE have been involved in identifying outcomes that are important to them as well as the diversity and therefore representativeness of PWLE recruited for studies. We consider why having more relevant outcomes could enhance the expertise of PWLE in managing their periodontitis. We then conclude with key learnings from our review which we hope will encourage more rapid development of these initiatives in periodontology for the benefit of global health and wellbeing.
Hierarchically Injectable Hydrogel Sequentially Delivers AntagomiR‐467a‐3p‐Loaded and AntagomiR‐874‐5p‐Loaded Satellite‐Cell‐Targeting Bioengineered Extracellular Vesicles Attenuating Sarcopenia
Authors: Hanhao Dai, Jun Luo, Lili Deng, Chao Song, Zhibo Deng, Yijing Wu, Song Gu, Jie Xu
Journal: Advanced Healthcare Materials (2023)

Sarcopenia is a geriatric disease characterized by reduced muscle function and mass. The capacity to self-renew and myogenesis of satellite cells (SCs) declines with age, resulting in age-related sarcopenia. MicroRNAs (miRNAs) can regulate the proliferation and myogenesis of SCs. In this study, it is identified that miR-467a-3p and miR-874-5p could respectively mediate the stemness and myogenesis of SCs by performing bioinformatics analysis. AntagomiR-467a-3p (ant-467a) and antagomiR-874-5p (ant-874) improve the stemness and myogenesis of SCs, respectively. SC-targeting extracellular vesicles (EVs) are constructed by overexpressing TSG101 on the surface of EVs isolated from bone marrow mesenchymal stem cells. Ant-467a loaded EVs (EVs-467a) and ant-874 loaded EVs (EVs-874) are prepared by transferring ant-467a and ant-874 into SC-targeting EVs. EVs-467a and EVs-874 are more effective than ant-467a and ant-874 in promoting the stemness and myogenesis of SCs. Sequentially intermuscular injection of EVs-467a and EVs-874 significantly improve sarcopenia in ovariectomy mice. The effects of multiple injections of EVs-467a and EVs-874 in the treatment of sarcopenia could be achieved by using a hierarchically injectable hydrogel to sustainedly release EVs-467a and EVs-874 in vivo. The findings provide an EV-based SC-targeting antagomiRNAs controlled release strategy as a novel therapy against sarcopenia.
COVID19 Impairs Cardiac Function via Endothelial H19 and IL6 Signaling
Authors: Rio P. Juni, Philippa G. Phelp, Diewertje I. Bink, Veerle Kremer, Anke S. van Bergen, Pedro Espinosa Gonzalez, Karlijn B. Rombouts, Karl J. Harber, Daan A.F. Heister, Kak K. Yeung, Jan Van den Bossche, Diederik W.D. Kuster, Paul A.J. Krijnen, Hans W.M. Niessen, Reinier A. Boon
Journal: Circulation Research (2023)
IL-10–producing Th1 cells possess a distinct molecular signature in malaria
Authors: Chelsea L. Edwards, Susanna S. Ng, Fabian de Labastida Rivera, Dillon Corvino, Jessica A. Engel, Marcela Montes de Oca, Luzia Bukali, Teija C.M. Frame, Patrick T. Bunn, Shashi Bhushan Chauhan, Siddharth Sankar Singh, Yulin Wang, Jinrui Na, Fiona H. Amante, Jessica R. Loughland, Megan S.F. Soon, Nicola Waddell, Pamela Mukhopadhay, Lambros T. Koufariotis, Rebecca L. Johnston, Jason S. Lee, Rachel Kuns, Ping Zhang, Michelle J. Boyle, Geoffrey R. Hill, James S. McCarthy, Rajiv Kumar, Christian R. Engwerda
Journal: Journal of Clinical Investigation (2023)
Molecular pathways that drive diabetic kidney disease
Authors: Samer Mohandes, Tomohito Doke, Hailong Hu, Dhanunjay Mukhi, Poonam Dhillon, Katalin Susztak
Journal: Journal of Clinical Investigation (2023)

Kidney disease is a major driver of mortality among patients with diabetes and diabetic kidney disease (DKD) is responsible for close to half of all chronic kidney disease cases. DKD usually develops in a genetically susceptible individual as a result of poor metabolic (glycemic) control. Molecular and genetic studies indicate the key role of podocytes and endothelial cells in driving albuminuria and early kidney disease in diabetes. Proximal tubule changes show a strong association with the glomerular filtration rate. Hyperglycemia represents a key cellular stress in the kidney by altering cellular metabolism in endothelial cells and podocytes and by imposing an excess workload requiring energy and oxygen for proximal tubule cells. Changes in metabolism induce early adaptive cellular hypertrophy and reorganization of the actin cytoskeleton. Later, mitochondrial defects contribute to increased oxidative stress and activation of inflammatory pathways, causing progressive kidney function decline and fibrosis. Blockade of the renin-angiotensin system or the sodium-glucose cotransporter is associated with cellular protection and slowing kidney function decline. Newly identified molecular pathways could provide the basis for the development of much-needed novel therapeutics.
Engineered Ferritin Nanoparticle Vaccines Enable Rapid Screening of Antibody Functionalization to Boost Immune Responses
Authors: Mai N. Vu, Emily H. Pilkington, Wen Shi Lee, Hyon‐Xhi Tan, Thomas P. Davis, Nghia P. Truong, Stephen J. Kent, Adam K. Wheatley
Journal: Advanced Healthcare Materials (2023)

Employing monoclonal antibodies to target vaccine antigens to different immune cells within lymph nodes where adaptive immunity is initiated can provide a mechanism to fine-tune the magnitude or the quality of immune responses. However, studying the effects of different targeting antibodies head-to-head is challenging due to the lack of a feasible method that allows rapid screening of multiple antibodies for their impact on immunogenicity. Here self-assembling ferritin nanoparticles are prepared that co-display vaccine antigens and the Fc-binding domain of Staphylococcal protein A, allowing rapid attachment of soluble antibodies to the nanoparticle surface. Using this tunable system, ten antibodies targeting different immune cell subsets are screened, with targeting to Clec9a associated with higher serum antibody titers after immunization. Immune cell targeting using ferritin nanoparticles with anti-Clec9a antibodies drives concentrated deposition of antigens within germinal centers, boosting germinal center formation and robust antibody responses. However, the capacity to augment humoral immunity is antigen-dependent, with significant boosting observed for prototypic ovalbumin immunogens but reduced effectiveness with the SARS-CoV-2 RBD. This work provides a rapid platform for screening targeting antibodies, which will accelerate mechanistic insights into optimal delivery strategies for nanoparticle-based vaccines to maximize protective immunity.